A novel approach for addressing diseases not yielding to effective vaccination? Immunization by replication-competent controlled virus

• Published in: Expert review of vaccines Vol. 14; no. 5; p. 637
• Main Authors: Voellmy, Richard, Bloom, David C, Vilaboa, Nuria
• Format: Journal Article
• Language: English
• Published: England 01.05.2015
• Subjects: Antigens - biosynthesis; Antigens - genetics; Antigens - immunology; Communicable Diseases - epidemiology; Communicable Diseases - transmission; Disease Transmission, Infectious - prevention & control; Humans; Immunization - methods; Virus Replication - radiation effects; Viruses - growth & development; Viruses - immunology; Viruses - radiation effects; heat-activated and ligand-activated gene switches; HSV; controlled replication; viral immunization agent; regulation of replication-essential genes; replication-competent virus; vaccination
• ISSN: 1744-8395
• DOI: 10.1586/14760584.2015.1013941

Vaccination involves inoculation of a subject with a disabled disease-causing microbe or parts thereof. While vaccination has been highly successful, we still lack sufficiently effective vaccines for important infectious diseases. We propose that a more complete immune response than that elicited from a vaccine may be obtained from immunization with a disease-causing virus modified to subject replication-essential genes to the control of a gene switch activated by non-lethal heat in the presence of a drug-like compound. Upon inoculation, strictly localized replication of the virus would be triggered by a heat dose administered to the inoculation site. Activated virus would transiently replicate with an efficiency approaching that of the disease-causing virus and express all viral antigens. It may also vector heterologous antigens or control co-infecting microbes.